Q9UBB5 (MBD2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Methyl-CpG-binding domain protein 2

Alternative name(s):
Demethylase
Short name=DMTase
Methyl-CpG-binding protein MBD2

Gene names

Name:

MBD2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	411 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Binds CpG islands in promoters where the DNA is methylated at position 5 of cytosine within CpG dinucleotides. Binds hemi-methylated DNA as well. Recruits histone deacetylases and DNA methyltransferases. Acts as transcriptional repressor and plays a role in gene silencing. Isoform 1 may enhance the activation of some unmethylated cAMP-responsive promoters. Reports about DNA demethylase activity of isoform 2 are contradictory. Ref.1 Ref.4 Ref.5 Ref.6 Ref.7 Ref.12
Subunit structure	Heterodimer with MBD3. Part of the MeCP1 complex that contains HDAC1 and HDAC2. Binds DNMT1, MIZF, GPN1, SIN3A, p66-alpha and p66-beta. Isoform 1 binds DHX9, but isoform 2 does not. Ref.6
Subcellular location	Nucleus. Note: Nuclear, in discrete foci. Detected at replication foci in late S phase. Ref.1 Ref.10
Tissue specificity	Highly expressed in brain, heart, kidney, stomach, testis and placenta. Ref.4
Sequence similarities	Contains 1 MBD (methyl-CpG-binding) domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Ligand	DNA-binding
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	C2H2 zinc finger domain binding Inferred from physical interaction Ref.9. Source: UniProtKB methyl-CpG binding Inferred from direct assay. Source: UniProtKB satellite DNA binding Traceable author statement. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9UBB5-1)

Also known as: MBD2a;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9UBB5-2)

Also known as: MBD2b;

The sequence of this isoform differs from the canonical sequence as follows:
     1-149: Missing.

Isoform 3 (identifier: Q9UBB5-3)

The sequence of this isoform differs from the canonical sequence as follows:
     235-302: GKPDLNTTLP...SDVTEQIIKT → LRWNTHRPAP...YSRQNQSFPP
     303-411: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 411

411

Methyl-CpG-binding domain protein 2

PRO_0000096260

Regions

Domain

145 – 213

69

MBD

Compositional bias

6 – 140

135

Gly-rich

Compositional bias

50 – 96

47

Arg-rich

Amino acid modifications

Modified residue

181

1

Phosphoserine Ref.14

Modified residue

407

1

Phosphoserine Ref.13 Ref.14 Ref.15 Ref.16

Natural variations

Alternative sequence

1 – 149

149

Missing in isoform 2.

VSP_011076

Alternative sequence

235 – 302

68

GKPDL…QIIKT → LRWNTHRPAPWHALSRLCLL IRCLLCLECAYPLPLHLVNS YSSKTQLHCLHLWEACPAYS RQNQSFPP in isoform 3.

VSP_011077

Alternative sequence

303 – 411

109

Missing in isoform 3.

VSP_011078

Secondary structure

1

.

.

.

.

411

Helix Strand Turn

Details...

Helix

366 – 388

23

Turn

389 – 392

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (MBD2a) [UniParc]. Last modified May 1, 2000. Version 1. Checksum: FC4E5E0CF9BA0FFA	FASTA	411	43,255
	10 20 30 40 50 60 MRAHPGGGRC CPEQEEGESA AGGSGAGGDS AIEQGGQGSA LAPSPVSGVR REGARGGGRG 70 80 90 100 110 120 RGRWKQAGRG GGVCGRGRGR GRGRGRGRGR GRGRGRPPSG GSGLGGDGGG CGGGGSGGGG 130 140 150 160 170 180 APRREPVPFP SGSAGPGPRG PRATESGKRM DCPALPPGWK KEEVIRKSGL SAGKSDVYYF 190 200 210 220 230 240 SPSGKKFRSK PQLARYLGNT VDLSSFDFRT GKMMPSKLQK NKQRLRNDPL NQNKGKPDLN 250 260 270 280 290 300 TTLPIRQTAS IFKQPVTKVT NHPSNKVKSD PQRMNEQPRQ LFWEKRLQGL SASDVTEQII 310 320 330 340 350 360 KTMELPKGLQ GVGPGSNDET LLSAVASALH TSSAPITGQV SAAVEKNPAV WLNTSQPLCK 370 380 390 400 410 AFIVTDEDIR KQEERVQQVR KKLEEALMAD ILSRAADTEE MDIEMDSGDE A
	Isoform 2 (MBD2b) [UniParc]. Checksum: 94C8932460BECE5B	FASTA	262	29,168
	10 20 30 40 50 60 MDCPALPPGW KKEEVIRKSG LSAGKSDVYY FSPSGKKFRS KPQLARYLGN TVDLSSFDFR 70 80 90 100 110 120 TGKMMPSKLQ KNKQRLRNDP LNQNKGKPDL NTTLPIRQTA SIFKQPVTKV TNHPSNKVKS 130 140 150 160 170 180 DPQRMNEQPR QLFWEKRLQG LSASDVTEQI IKTMELPKGL QGVGPGSNDE TLLSAVASAL 190 200 210 220 230 240 HTSSAPITGQ VSAAVEKNPA VWLNTSQPLC KAFIVTDEDI RKQEERVQQV RKKLEEALMA 250 260 DILSRAADTE EMDIEMDSGD EA
	Isoform 3 [UniParc]. Checksum: CCEC65D926222717	FASTA	302	31,745
	10 20 30 40 50 60 MRAHPGGGRC CPEQEEGESA AGGSGAGGDS AIEQGGQGSA LAPSPVSGVR REGARGGGRG 70 80 90 100 110 120 RGRWKQAGRG GGVCGRGRGR GRGRGRGRGR GRGRGRPPSG GSGLGGDGGG CGGGGSGGGG 130 140 150 160 170 180 APRREPVPFP SGSAGPGPRG PRATESGKRM DCPALPPGWK KEEVIRKSGL SAGKSDVYYF 190 200 210 220 230 240 SPSGKKFRSK PQLARYLGNT VDLSSFDFRT GKMMPSKLQK NKQRLRNDPL NQNKLRWNTH 250 260 270 280 290 300 RPAPWHALSR LCLLIRCLLC LECAYPLPLH LVNSYSSKTQ LHCLHLWEAC PAYSRQNQSF PP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification and characterization of a family of mammalian methyl-CpG binding proteins." Hendrich B., Bird A. Mol. Cell. Biol. 18:6538-6547(1998) [PubMed: 9774669] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), FUNCTION, SUBCELLULAR LOCATION. Tissue: Testis.
[2]	"Genomic structure and chromosomal mapping of the murine and human mbd1, mbd2, mbd3, and mbd4 genes." Hendrich B., Abbott C., McQueen H., Chambers D., Cross S.H., Bird A. Mamm. Genome 10:906-912(1999) [PubMed: 10441743] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Lymph.
[4]	"A mammalian protein with specific demethylase activity for mCpG DNA." Bhattacharya S.K., Ramchandani S., Cervoni N., Szyf M. Nature 397:579-583(1999) [PubMed: 10050851] [Abstract] Cited for: FUNCTION (ISOFORM 2), TISSUE SPECIFICITY.
[5]	"MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase complex." Ng H.-H., Zhang Y., Hendrich B., Johnson C.A., Turner B.M., Erdjument-Bromage H., Tempst P., Reinberg D., Bird A. Nat. Genet. 23:58-61(1999) [PubMed: 10471499] [Abstract] Cited for: FUNCTION, MASS SPECTROMETRY, INTERACTION WITH MECP1 AND HDAC1.
[6]	"MBD2-MBD3 complex binds to hemi-methylated DNA and forms a complex containing DNMT1 at the replication foci in late S phase." Tatematsu K., Yamazaki T., Ishikawa F. Genes Cells 5:677-688(2000) [PubMed: 10947852] [Abstract] Cited for: FUNCTION, HETERODIMERIZATION WITH MBD3, INTERACTION WITH DNMT1.
[7]	"The minimal repression domain of MBD2b overlaps with the methyl-CpG-binding domain and binds directly to Sin3A." Boeke J., Ammerpohl O., Kegel S., Moehren U., Renkawitz R. J. Biol. Chem. 275:34963-34967(2000) [PubMed: 10950960] [Abstract] Cited for: FUNCTION (ISOFORM 2), INTERACTION WITH SIN3A.
[8]	"Stable histone deacetylase complexes distinguished by the presence of SANT domain proteins CoREST/kiaa0071 and Mta-L1." Humphrey G.W., Wang Y., Russanova V.R., Hirai T., Qin J., Nakatani Y., Howard B.H. J. Biol. Chem. 276:6817-6824(2001) [PubMed: 11102443] [Abstract] Cited for: INTERACTION WITH HDAC1, MASS SPECTROMETRY.
[9]	"Involvement of a novel zinc finger protein, MIZF, in transcriptional repression by interacting with a methyl-CpG-binding protein, MBD2." Sekimata M., Takahashi A., Murakami-Sekimata A., Homma Y. J. Biol. Chem. 276:42632-42638(2001) [PubMed: 11553631] [Abstract] Cited for: INTERACTION WITH MIZF.
[10]	"Two highly related p66 proteins comprise a new family of potent transcriptional repressors interacting with MBD2 and MBD3." Brackertz M., Boeke J., Zhang R., Renkawitz R. J. Biol. Chem. 277:40958-40966(2002) [PubMed: 12183469] [Abstract] Cited for: INTERACTION WITH P66ALPHA AND P66BETA, SUBCELLULAR LOCATION.
[11]	"MBDin, a novel MBD2-interacting protein, relieves MBD2 repression potential and reactivates transcription from methylated promoters." Lembo F., Pero R., Angrisano T., Vitiello C., Iuliano R., Bruni C.B., Chiariotti L. Mol. Cell. Biol. 23:1656-1665(2003) [PubMed: 12588985] [Abstract] Cited for: INTERACTION WITH GPN1.
[12]	"Antithetic effects of MBD2a on gene regulation." Fujita H., Fujii R., Aratani S., Amano T., Fukamizu A., Nakajima T. Mol. Cell. Biol. 23:2645-2657(2003) [PubMed: 12665568] [Abstract] Cited for: FUNCTION, INTERACTION WITH DHX9.
[13]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-407, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[14]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181 AND SER-407, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[15]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-407, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[16]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-407, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF072242 mRNA. Translation: AAC68871.1.
AF072246 mRNA. Translation: AAC68875.1.
AF120989, AF120988 Genomic DNA. Translation: AAD56596.1.
AF120993 , AF120988, AF120989, AF120990, AF120991, AF120992 Genomic DNA. Translation: AAD56597.1.
BC032638 mRNA. Translation: AAH32638.1.

IPI

IPI00434623.
IPI00434624.
IPI00434625.

RefSeq

NP_003918.1. NM_003927.4.
NP_056647.1. NM_015832.4.

UniGene

Hs.25674.
Hs.600072.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2L2L	NMR	-	B	360-393	[»]

ProteinModelPortal

Q9UBB5.

SMR

Q9UBB5. Positions 149-213, 360-393.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9UBB5. 5 interactions.

STRING

Q9UBB5.

PTM databases

PhosphoSite

Q9UBB5.

Polymorphism databases

DMDM

50401198.

Proteomic databases

PRIDE

Q9UBB5.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000256429; ENSP00000256429; ENSG00000134046.

GeneID

8932.

KEGG

hsa:8932.

UCSC

uc002lfg.1. human.
uc002lfh.1. human.

Organism-specific databases

CTD

8932.

GeneCards

GC18M051615.

H-InvDB

HIX0018044.

HGNC

HGNC:6917. MBD2.

HPA

CAB037282.

MIM

603547. gene.

neXtProt

NX_Q9UBB5.

PharmGKB

PA30660.

GenAtlas

Search...

Phylogenomic databases

GeneTree

ENSGT00410000025376.

HOGENOM

HBG315648.

HOVERGEN

HBG052417.

InParanoid

Q9UBB5.

OMA

DTEEVDI.

OrthoDB

EOG4GF3FS.

PhylomeDB

Q9UBB5.

Enzyme and pathway databases

Pathway_Interaction_DB

hdac_classi_pathway. Signaling events mediated by HDAC Class I.

Gene expression databases

ArrayExpress

Q9UBB5.

Bgee

Q9UBB5.

CleanEx

HS_MBD2.

Genevestigator

Q9UBB5.

GermOnline

ENSG00000134046. Homo sapiens.

Family and domain databases

InterPro

IPR016177. DNA-bd_integrase-typ.
IPR001739. Methyl_CpG_DNA-bd.
[Graphical view]

Gene3D

G3DSA:3.30.890.10. Methyl_CpG_DNA-bd. 1 hit.

KO

K11590.

Pfam

PF01429. MBD. 1 hit.
[Graphical view]

SMART

SM00391. MBD. 1 hit.
[Graphical view]

SUPFAM

SSF54171. DNA-binding_integrase-type. 1 hit.

PROSITE

PS50982. MBD. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB01355. Hexobarbital.

NextBio

33582.

SOURCE

Search...

Entry information

Entry name

MBD2_HUMAN

Accession

Primary (citable) accession number: Q9UBB5
Secondary accession number(s): O95242, Q9UIS8

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 19, 2004
Last sequence update:	May 1, 2000
Last modified:	January 25, 2012
This is version 100 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.